Objective:To compare normative ventilatory and gas-exchange data and anesthetic requirements in male and female rats subjected to critical care conditions.Design:Prospective study.Setting:Critical care research laboratory in a hospital.Subjects:Twenty-two age-matched young male and female rats (Sprague-Dawley, Long Evans strain).Interventions:Anesthesia was induced with 65 and 45 mg/kg pentobarbital in male and female rats, respectively. The rats were then tracheostomized and cannulated in one femoral vein and artery. Anesthesia was maintained using 8-15 mg/kg/hr pentobarbital (iv) and controlled by continuous hemodynamic monitoring.Measurements and Main Results:Normoxic baselines for breathing frequency, tidal volume, minute volume, inspiratory-to-expiratory ratio, inspiratory drive (tidal volume/inspiratory time), respiratory system compliance, peak airway pressure, and gas-exchange profiles were established. Ventilatory and gas-exchange responses to oxygen and CO2were then determined by exposure to 10 mins of hyperoxia (100% oxygen), two levels of mild and severe hypercapnic hyperoxia (inspired PCO2of 30 and 60 torr; 4 and 8 kPa), and two levels of mild and severe normocapnic hypoxia (inspired PO2of 81 and 48 torr; 10.7 and 6.3 kPa). The average anesthetic requirement (during a 5- to 6-hr experiment) was 30% less in the female rats than in the male rats (p< .05). Female rats showed significantly lower breathing frequency, minute volume (mL/min/kg), and inspiratory drive (mL/kg/sec) during hyperoxia, mild and severe hypercapnia, and mild hypoxia. Pulmonary peak airway pressure was significantly lower in the female rats, consistent with a significantly higher weight-indexed compliance during all exposures. The female rats also had significantly higher inspiratory-to-expiratory ratio and higher PaCO2with lower pH during normoxia, hyperoxia, and mild hypercapnia. These gender differences had no effect on PaO2, which was similar in all exposures.Conclusions:There are significant gender differences in ventilation, gas exchange, and anesthetic requirements in rats subjected to critical care conditions. The gas-exchange values observed in these spontaneously breathing rats may represent the optimal levels attainable during pentobarbital anesthesia with normal lungs. They may serve as standards for ventilator settings in the rat models used for critical care studies.